The systemic metabolism of the neurotransmitter GABA was investigated under normal and coma conditions. The plasma levels of GABA are known to be elevated by an order of magnitude over normal in patients with coma resulting from fulminant hepatic failure. To investigate the mechanism(s) for this elevation, a kinetic model was developed to describe GABA metabolism during various stages of coma in a rabbit model. The major finding of the analysis was that a defect in GABA catabolism could not explain the elevations in plasma levels and additional sources for GABA production must be postulated. Subsequent experimental studies have supported these results by showing that gut bacterial production of GABA is substantially elevated during hepatic coma.